Legal and professional implications of shared care: a case study in oral anticoagulation stroke prevention therapy.

Policy initiatives and technological advances enable the use of integrated shared care models of healthcare delivery whereby the focus of care is moved from the hospital to the community, and also of models where patients take increasing responsibility for monitoring and treatment. Such shifts may or may be perceived to change professional roles and responsibilities with implications to the delivery of a professionally and legally acceptable standard of care. We focus on oral anticoagulation and stroke prevention therapy to examine some possible professional and legal implications of the increasing use of shared care

Maintenance treatment for recurrent ovarian carcinoma – Evidence supporting the efficacy and safety of PARP inhibitors

While recent advances in treatment mean that women with ovarian cancer are living longer, many eventually experience disease relapse highlighting the need for new treatments that can extend progression-free survival (PFS). The PARP inhibitors olaparib, niraparib and rucaparib have been approved by the US Food and Drug Administration and the European Commission and are currently available for the maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. Here, we review the efficacy and safety data from the key clinical trials supporting the approvals for these treatments as second-line maintenance therapies, including Study 19, SOLO2/ ENGOT-OV21 (olaparib), NOVA/ENGOT-OV16 (niraparib) and ARIEL3 (rucaparib). Across trials, PFS was improved with PARP inhibitor maintenance treatment versus placebo in patients with a BRCA mutation. However, evidence from some of the trials shows that a wider group of patients can benefit from PARP inhibitor maintenance treatment including those with or without homologous recombination deficient tumours. The safety profile for olaparib, niraparib and rucaparib was generally similar across trials with haematological and gastrointestinal adverse events and fatigue/asthenia being the most common. As evidenced by the significant improvements in PFS and manageable safety profiles in these trials, PARP inhibitors represent a new standard of care for recurrent ovarian cancer following platinum-based chemotherapy and delay the need for further chemotherapy

Sound field planarity characterized by superdirective beamforming

The ability to replicate a plane wave represents an essential element of spatial sound field reproduction. In sound field synthesis, the desired field is often formulated as a plane wave and the error minimized; for other sound field control methods, the energy density or energy ratio is maximized. In all cases and further to the reproduction error, it is informative to characterize how planar the resultant sound field is. This paper presents a method for quantifying a region's acoustic planarity by superdirective beamforming with an array of microphones, which analyzes the azimuthal distribution of impinging waves and hence derives the planarity. Estimates are obtained for a variety of simulated sound field types, tested with respect to array orientation, wavenumber, and number of microphones. A range of microphone configurations is examined. Results are compared with delay-and-sum beamforming, which is equivalent to spatial Fourier decomposition. The superdirective beamformer provides better characterization of sound fields, and is effective with a moderate number of omni-directional microphones over a broad frequency range. Practical investigation of planarity estimation in real sound fields is needed to demonstrate its validity as a physical sound field evaluation measure. © 2013 Acoustical Society of America

Up and away: ontogenic transference as a pathway for aerial dispersal of microplastics

Microplastics (MPs) are ubiquitous pollutants found in marine, freshwater and terrestrial ecosystems. With so many MPs in aquatic systems it is inevitable that they will be ingested by aquatic organisms, and be transferred up through the food chain. However, to date, no study has considered whether MPs can be transmitted by means of ontogenic transference i.e. between life stages that utilise different habitats. Here, we determine whether fluorescent polystyrene beads could transfer between Culex mosquito life stages and, particularly, could move into the flying adult stage. We show for the first time that MPs can be transferred ontogenically from a feeding (larva) into a non-feeding (pupa) life stage and subsequently into the adult terrestrial life stage. However, transference is dependent on particle size, with smaller 2 µm MPs transferring readily into pupae and adult stages, whilst 15 µm MPs transferred at a significantly reduced rate. Microplastics appear to accumulate in the Malpighian tubule renal excretion system. The transfer of MPs to the adults represents a potential aerial pathway to contamination of new environments. Thus, any organism that feeds on terrestrial life phases of freshwater insects could be impacted by MPs found in aquatic ecosystems

Higher-order scalar interactions and SM vacuum stability

Investigation of the structure of the Standard Model effective potential at very large field strengths opens a window towards new phenomena and can reveal properties of the UV completion of the SM. The map of the lifetimes of the vacua of the SM enhanced by nonrenormalizable scalar couplings has been compiled to show how new interactions modify stability of the electroweak vacuum. Whereas it is possible to stabilize the SM by adding Planck scale suppressed interactions and taking into account running of the new couplings, the generic effect is shortening the lifetime and hence further destabilisation of the SM electroweak vacuum. These findings have been illustrated with phase diagrams of modified SM-like models. It has been demonstrated that stabilisation can be achieved by lowering the suppression scale of higher order operators while picking up such combinations of new couplings, which do not deepen the new minima of the potential. Our results show the dependence of the lifetime of the electroweak minimum on the magnitude of the new couplings, including cases with very small couplings (which means very large effective suppression scale) and couplings vastly different in magnitude (which corresponds to two different suppression scales).Comment: plain Latex, 9 figure

The break up of heavy electrons at a quantum critical point

The point at absolute zero where matter becomes unstable to new forms of order is called a quantum critical point (QCP). The quantum fluctuations between order and disorder that develop at this point induce profound transformations in the finite temperature electronic properties of the material. Magnetic fields are ideal for tuning a material as close as possible to a QCP, where the most intense effects of criticality can be studied. A previous study on theheavy-electron material $YbRh_2Si_2$ found that near a field-induced quantum critical point electrons move ever more slowly and scatter off one-another with ever increasing probability, as indicated by a divergence to infinity of the electron effective mass and cross-section. These studies could not shed light on whether these properties were an artifact of the applied field, or a more general feature of field-free QCPs. Here we report that when Germanium-doped $YbRh_2Si_2$ is tuned away from a chemically induced quantum critical point by magnetic fields there is a universal behavior in the temperature dependence of the specific heat and resistivity: the characteristic kinetic energy of electrons is directly proportional to the strength of the applied field. We infer that all ballistic motion of electrons vanishes at a QCP, forming a new class of conductor in which individual electrons decay into collective current carrying motions of the electron fluid.Comment: Pdf files of article available at http://www.physics.rutgers.edu/~coleman/online/breakup.pdf, pdf file of news and views article available at http://www.physics.rutgers.edu/~coleman/online/nvbreakup.pd

Sparse Coding Predicts Optic Flow Specificities of Zebrafish Pretectal Neurons

Zebrafish pretectal neurons exhibit specificities for large-field optic flow patterns associated with rotatory or translatory body motion. We investigate the hypothesis that these specificities reflect the input statistics of natural optic flow. Realistic motion sequences were generated using computer graphics simulating self-motion in an underwater scene. Local retinal motion was estimated with a motion detector and encoded in four populations of directionally tuned retinal ganglion cells, represented as two signed input variables. This activity was then used as input into one of two learning networks: a sparse coding network (competitive learning) and backpropagation network (supervised learning). Both simulations develop specificities for optic flow which are comparable to those found in a neurophysiological study (Kubo et al. 2014), and relative frequencies of the various neuronal responses are best modeled by the sparse coding approach. We conclude that the optic flow neurons in the zebrafish pretectum do reflect the optic flow statistics. The predicted vectorial receptive fields show typical optic flow fields but also "Gabor" and dipole-shaped patterns that likely reflect difference fields needed for reconstruction by linear superposition.Comment: Published Conference Paper from ICANN 2018, Rhode

Field-induced quantum fluctuations in the heavy fermion superconductor CeCu2Ge2

Quantum-mechanical fluctuations in strongly correlated electron systems cause unconventional phenomena such as non-Fermi liquid behavior, and arguably high temperature superconductivity. Here we report the discovery of a field-tuned quantum critical phenomenon in stoichiometric CeCu2Ge2, a spin density wave ordered heavy fermion metal that exhibits unconventional superconductivity under ~ 10 GPa of applied pressure. Our finding of the associated quantum critical spin fluctuations of the antiferromagnetic spin density wave order, dominating the local fluctuations due to single-site Kondo effect, provide new information about the underlying mechanism that can be important in understanding superconductivity in this novel compound.Comment: Heavy Fermion, Quantum Critical Phenomeno

Chemical and structural investigation of the paroxetine-human serotonin transporter complex

Antidepressants target the serotonin transporter (SERT) by inhibiting serotonin reuptake. Structural and biochemical studies aiming to understand binding of small-molecules to conformationally dynamic transporters like SERT often require thermostabilizing mutations and antibodies to stabilize a specific conformation, leading to questions about relationships of these structures to the bonafide conformation and inhibitor binding poses of wild-type transporter. To address these concerns, we determined the structures of ∆N72/∆C13 and ts2-inactive SERT bound to paroxetine analogues using single-particle cryo-EM and x-ray crystallography, respectively. We synthesized enantiopure analogues of paroxetine containing either bromine or iodine instead of fluorine. We exploited the anomalous scattering of bromine and iodine to define the pose of these inhibitors and investigated inhibitor binding to Asn177 mutants of ts2-active SERT. These studies provide mutually consistent insights into how paroxetine and its analogues bind to the central substrate-binding site of SERT, stabilize the outward-open conformation, and inhibit serotonin transport